A Phase IIa Randomized, Double-Blind Trial of Erlotinib in Inhibiting EGF Receptor Signaling in Aberrant Crypt Foci of the Colon

Inclusion Criteria:

- Participants with one or more of the following criteria will be eligible to
participate:

- History of Stage I-III colorectal cancer, not treated in the past 6 months with
no anticipated treatment in the next 3 months

- Adenoma ≥ 1 cm in size

- 3 or more adenomas (of any size) removed at one colonoscopy within past 6 years

- Sessile serrated adenoma ≥ 5 mm in size

- Adenoma (of any size) with villous features (villous, tubulovillous)

- Adenoma (of any size) with high grade dysplasia

- Participants are eligible for randomization into the treatment phase of the trial if
they are found to have ≥ 4 ACFs at either baseline colonoscopy or baseline flexible
sigmoidoscopy

- Blood tests at screening which meet the following criteria:

- WBC > 3000/mm^3

- Platelets > 100,000/mm^3

- Hemoglobin > 10g/dl

- Plasma creatinine of < 1.6mg/dl

- Total bilirubin < 1.5 x the upper limit of normal

- Serum ALT < 1.5 x the upper limit of normal

- Serum AST < 1.5 x the upper limit of normal

- ECOG performance status 0-1

- Women of child-bearing potential and men taking study drug must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation

- Ability to understand, as well as sign the written informed consent document

- If a woman is of child-bearing potential, she must have a negative pregnancy test
prior to study entry; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her study physician immediately

Exclusion Criteria:

- History of Inflammatory Bowel Disease (IBD)

- History of interstitial lung disease or chronic lung disease

- Smoking within the past 3 months

- Increased bleeding risk from rectal biopsy (Patients receiving aspirin or plavix can
be enrolled)

- Patients receiving warfarin or coumadin

- Uncontrollable diarrhea of any cause

- Patients, including rectal cancer patients, that have received prior radiation to the
rectum or pelvis

- Participants taking a known significant CYP 3A4 inducer or inhibitor; known
significant inducers/inhibitors include: amprenavir, aprepitant, atazanavir,
carbamazepine, clarithromycin, conivaptan, diltiazem, darunavir/ritonavir,
dronedarone, erythromycin, fluconazole, fosamprenavir, indinavir, itraconazole,
ketoconazole, nefazodone, nelfinavir, phenytoin, posaconazole, rifampin, ritonavir,
St. John's wort, saquinavir, telithromycin, tipranavir/ritonavir, verapamil,
voriconazole

- Women who are pregnant or breast-feeding

- Active keratoconjunctivitis, or corneal surgery in the past three weeks

- Any medical or psychosocial condition that could jeopardize the subject's
participation in and compliance to the study

- Participants who are taking any other investigational pharmaceutical agents

- Previous history of sensitivity to erlotinib, Iressa, or Erbitux, such as a rash that
is uncontrollable by topical steroids and/or antibiotics